A Unique Paradigm for a Turn-ON Near-Infrared Cyanine-Based Probe: Noninvasive Intravital Optical Imaging of Hydrogen Peroxide

• Published in: Journal of the American Chemical Society Vol. 133; no. 28; pp. 10960 - 10965
• Main Authors: Karton-Lifshin, Naama, Segal, Ehud, Omer, Liora, Portnoy, Moshe, Satchi-Fainaro, Ronit, Shabat, Doron
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.07.2011; Amer Chemical Soc
• Subjects: Animals; Carbocyanines - metabolism; Chemistry; Chemistry, Multidisciplinary; Fluorescent Dyes - metabolism; Hydrogen Peroxide - metabolism; Infrared Rays; Mice; Molecular Imaging - methods; Optical Phenomena; Physical Sciences; Science & Technology; FLUORESCENT-PROBES; MOLECULAR PROBE; DYES; SENSORS; IN-VIVO
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja203145v

The development of highly sensitive fluorescent probes in combination with innovative optical techniques is a promising strategy for intravital noninvasive quantitative imaging. Cyanine fluorochromes belong to a superfamily of dyes that have attracted substantial attention in probe design for molecular imaging. We have developed a novel paradigm to introduce a Turn-ON mechanism in cyanine molecules, based on a distinctive change in their π-electrons system. Our new cyanine fluorochrome is synthesized through a simple two-step procedure and has an unprecedented high fluorescence quantum yield of 16% and large extinction coefficient of 52 000 M–1cm–1. The synthetic strategy allows one to prepare probes for various analytes by introducing a specific triggering group on the probe molecule. The probe was equipped with a corresponding trigger and demonstrated efficient imaging of endogenous hydrogen peroxide, produced in an acute lipopolysaccharide-induced inflammation model in mice. This approach provides, for the first time, an available methodology to prepare modular molecular Turn-ON probes that can release an active cyanine fluorophore upon reaction with specific analyte.